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The drug, Keytruda (pembrolizumab), was tested on more than 600 patients who had melanoma that had spread throughout their bodies. Because so many of the patients in the early testing showed significant long-lasting responses, the study was continued and the FDA granted the drug “breakthrough therapy” status, allowing it to be fast-tracked for approval.

The largest Phase 1 study in the history of oncology, the research was conducted at UCLA and 11 other sites in the U.S., Europe and Australia.

Keytruda, formerly known as MK-3475, is an antibody that targets a protein called PD-1 that is expressed by immune cells. The protein puts the immune system’s brakes on, keeping its T cells from recognizing and attacking cancer cells, said Dr. Antoni Ribas, the study’s principal investigator and a professor of medicine in the division of hematology-oncology at the David Geffen School of Medicine at UCLA.

For many years, when using immunotherapy to fight cancer, doctors’ strategy has been to bolster the immune system so it could kill the cancer cells. But the approach had limited success because PD-1 prevented the immune system from becoming active enough to attack the cancer.

Keytruda, in effect, cuts the brake lines, freeing up the immune system to attack the cancer.

“This drug is a game changer, a very significant advance in the treatment of melanoma,” said Ribas, who also is a researcher at UCLA’s Jonsson Comprehensive Cancer Center. “For patients who have not responded to prior therapies, this drug now provides a very real chance to shrink their tumors and the hope of a lasting response to treatment.”

Judith Gasson, senior associate dean for research at the David Geffen School of Medicine at UCLA and director of the Jonsson Cancer Center, said researchers have long hoped to develop an effective and lasting immunotherapy to fight cancer.

“We have long believed that harnessing the power of our own immune systems would dramatically alter cancer treatment,” she said. “Based upon work conducted over the past two decades, we are beginning to see the clinical benefits of this research in some of the most challenging cancers.”

Generally, about 1 in 10 patients responded to previous immunotherapy drugs. Some of those who responded, however, exhibited long-lived benefits, which sustained scientists’ interest in the method as an effective mechanism to fight cancer.

The response and duration rates for Keytruda were much greater than for previous drugs, Ribas said. In the new study, 72 percent of patients responded to the drug, meaning that their tumors shrank to some degree. Overall, 34 percent of patients showed an objective response, meaning that their tumors shrank by more than 30 percent, and did not re-grow.

Ribas said Keytruda has the potential to be used to treat other cancers that the immune system can recognize, including cancers of the lung, bladder, head and neck.

Survivors’ stories Kathy Thomas, 59, of Torrance, California, was diagnosed in September 2011 with melanoma that had spread to her liver and was invading her left breast. She underwent several therapies that did not work, and she was weakening fast.

“I lost weight. I threw up nearly every day,” Thomas said. “My hair was thinning. I just had no strength at all. I was so sick I had to use a wheelchair.”

Thomas met with Ribas in 2012 but was skeptical about enrolling in a trial to test an experimental therapy. She soon overcame her hesitation.

Since enrolling in the study, Thomas’ tumors have shrunk. She regained her strength and her appetite. She’s out of her wheelchair and walking normally again. She said she has experienced no side effects from the therapy, and she travels monthly to San Francisco to visit her grandson.

Tom Stutz, 74, of Sherman Oaks, California, was diagnosed in June 2011 with melanoma that had spread to his lung, liver and other parts of his body. He didn’t see how he could survive, but he decided to enroll in the clinical trial of Keytruda anyway.

“I wasn’t eating. I was on oxygen. I couldn’t walk,” he said. “When I went into the hospital at the end of May [2012], I didn’t think I was coming out.”

Gradually, though, Stutz started feeling better. Today, he’s no longer on oxygen and walks several miles every day.

“It’s the little things that make me happy now,” Stutz said. “I’m very appreciative that I get to get up in the morning, go into my backyard and see my garden. I’m able to be with my children and grandchildren, go on vacations with them. I was close to the end of the road, as far as you can get to the edge of the cliff, and I was pulled back by this treatment.”

Melanoma incidence rates have been increasing for at least 30 years. An estimated 76,100 new cases of melanoma will be diagnosed in the U.S. in 2014, and nearly 10,000 Americans will die from the disease this year. While melanoma accounts for less than 2 percent of all skin cancer cases, it is responsible for the vast majority of skin cancer deaths, according to the American Cancer Society.

The researchers, whose results were published today in Cell, successfully grew six prostate cancer organoids from biopsies of patients with metastatic prostate cancer and a seventh organoid from a patient’s circulating tumor cells. Organoids are three-dimensional structures composed of cells that are grouped together and spatially organized like an organ. The histology, or tissue structure, of the prostate cancer organoids is highly similar to the metastasis sample from which they came. Sequencing of the metastasis samples and the matched organoids showed that each organoid is genetically identical to the patient’s cancer from which it originated.

“Identifying the molecular biomarkers that indicate whether a drug will work or why a drug stops working is paramount for the precision treatment of cancer,” said Yu Chen, MD, PhD, Assistant Attending Physician in the Genitourinary Oncology Service and Human Oncology and Pathogenesis Program at MSK. “But we are limited in our capacity to test drugs — especially in the prostate cancer setting, where only a handful of prostate cancer cell lines are available to researchers.”

With the addition of the seven prostate cancer organoids described in the Cell paper, Dr. Chen’s team has effectively doubled the number of existing prostate cancer cell lines.

“We now have a new resource at our disposal that captures the molecular diversity of prostate cancer. This will be an invaluable tool we can use to test drug sensitivity,” he added.

The use of organoids in studying cancer is relatively new, but the field is exploding quickly according to Dr. Chen. In 2009, Hans Clevers, MD, PhD, of the Hubrecht Institute in the Netherlands demonstrated that intestinal stem cells could form organoids. Dr. Clevers is the lead author on a companion piece also published in Cell today that describes how to create healthy prostate organoids. Dr. Chen’s paper is the first to demonstrate that organoids can be grown from prostate cancer samples.

The prostate cancer organoids can be used to test multiple drugs simultaneously, and Dr. Chen’s team is already retrospectively comparing the drugs given to each patient against the organoids for clues about why the patient did or didn’t respond to therapy. In the future, it’s possible that drugs could be tested on a patient’s organoid before being given to the patient to truly personalize treatment.

After skin cancer, prostate cancer is the most common cancer in American men — about 233,000 new cases will be diagnosed in 2014. It is also the second leading cause of cancer death in men; 1 in 36 men will die of the disease.

Despite its prevalence, prostate cancer has been difficult to replicate in the lab. Many mutations that play a role in its growth are not represented in the cell lines currently available. Cell lines can also differ from their original source, and because they are composed of single cells, they do not offer the robust information that an organoid — which more closely resembles a living organ — can provide.

The University of Lincoln’s Professor Nigel Allinson MBE will deliver the keynote talk at the tenth International Conference on Position Sensitive Detectors. The conference, which takes place from 7th to 12th September 2014, features the latest developments in this field from leading researchers around the world.

Professor Allinson leads the pioneering PRaVDA (Proton Radiotherapy Verification and Dosimetry Applications) project. He and his multinational team are developing one of the most complex medical instruments ever imagined to improve the delivery of proton beam therapy in the treatment of cancer.

Proton beam therapy is a type of particle therapy that uses a beam of protons to irradiate diseased tissue. Proton beam therapy has the ability to deliver high doses of radiation directly to a tumour site with very little radiation being absorbed into healthy tissue.

PRaVDA, funded by a £1.6 million grant from the Wellcome Trust, will provide a unique instrument capable of producing real-time 3D images — a proton CT — of a patient, drawing data from the same protons used in the treatment itself.

The patent-pending technology, which uses detectors at the heart of the Large Hadron Collider at CERN alongside world-first radiation-hard CMOS imagers, will reduce dose uncertainties from several centimetres to just a few millimetres.

This promises to make proton therapy an option for thousands more cancer patients by reducing the risks of healthy tissue being damaged during treatment, particularly in vulnerable parts of the body such as the brain, eye and spinal cord.

Professor Allinson, who will also be talking about his research to prospective students at the University of Lincoln open day on Saturday, 20th September, said: “PRaVDA will ensure more difficult tumours will become treatable and more patients overall will be able to receive this revolutionary treatment.”

Other members of the PRaVDA team will also present their work at the conference, describing in more detail the high-speed tracking technology that can record the paths of individual protons as they enter and leave a patient. The team will also outline how they make and test the new detectors in PRaVDA to ensure they are resistant to the high levels of radiation present in proton therapy.

The researchers have just taken delivery of some of the technology which will lie at the heart of the system: two state-of-the-art custom integrated circuits (chips) which will underpin PRaVDA’s imaging capabilities.

One device is a radiation-hard CMOS imager, measuring 10cm x 6.5cm, and producing more than 1,500 images per second. The camera chip in a mainstream smartphone is a CMOS imager but PRaVDA’s chip is over 300 times larger and operates 50 times faster — the fastest large-area CMOS imager ever made. The completed PRaVDA instrument will contain 48 of these imagers, giving a total imaging area of nearly two-and-a-half square metres.

The second device is the read-out chip for the very high-speed strip detectors that track the passage of individual protons as they enter and exit a patient. This chip, called Rhea, converts the electric charge created by a passing proton into a digital signal with additional logic to provide accurate timing (to one hundredth of one millionth of a second) while preventing erroneous signals being recorded.

The strip detectors were designed at the University of Liverpool by the same team that developed detectors for the Large Hadron Collider at CERN, which led to the discovery of the Higgs Boson in 2013. Nearly 200 Rheas are used in the complete PRaVDA system.

PRaVDA’s industrial partner, ISDI LTD, designed both devices. Their testing was undertaken by the project’s second industrial partner, aSpect Systems GmbH, in Dresden, Germany.